Current research activities employ contrast-enhancing agents in conjunction with ultrasound imaging to improve the visualization of the perfusion of internal organs. The contrast agents are often configured as microbubbles that comprise a shell which acts to contain an internal gas or other contrast enhancing agent. For instance, perfluorocarbon-exposed sonicated dextrose albumin microbubbles have been employed to improve the contrast of ultrasound images. Typically, these microbubbles can be destroyed if sufficiently high levels of ultrasonic energy are applied.
One disadvantage of utilizing such contrast-enhancing agents is that the scattering of acoustic energy which results from their presence causes a reduction of transmitted acoustic energy therethrough. As a result, structures that lie distally to an area that has been perfused with a microencapsulated contrast agent are "shadowed" by the contrast enhancing agent. For instance, when such a contrast agent is administered to the heart, while attempting to image the perfusion of the arterial structures of the myocardium, the left ventricle blood pool will substantially shadow the distally located myocardial wall structure.
Porter et al. have reported upon use of a transient imaging technique which utilizes contrast enhancing microbubble agents. See: "Transient Myocardial Contrast After Initial Exposure to Diagnostic Ultrasound Pressures with Minute Doses of Intravenously Injected Microbubbles", Circulation, Volume 92, (1995), pages 2391-2395. In particular, Porter et al. administered contrast enhancing microbubbles to the hearts of dogs and then subsequently measured myocardial contrast during triggered ultrasound imaging cycles (i.e., one scan per cardiac cycle). Further, they withheld real-time ultrasound transmission until after microbubbles had entered the myocardium, after intravenous injection.
Porter et al. reported that the transient imaging produced significantly greater myocardial contrast than continuous imaging. One rationale presented for the improved imaging was that the standard-imaging pulse rates destroyed the microbubbles. By delaying ultrasound transmission or triggering pulses to one part of the cardiac cycle, more bubbles were enabled to reach the myocardium and hence caused greater contrast.
In utilizing encapsulated contrast agents, it would be useful to cause destruction of the microbubbles (and thus a significant reduction in the ultrasound shadowing effect created thereby) by selectively timing destruction of the microbubbles so as to enable subsequent imaging of distally located regions which also contain the contrast agent microbubbles.
In addition to the use of contrast agent microbubbles, investigators have proposed the encapsulation of a therapeutic into microbubbles. To assure enhanced effectiveness of the encapsulated therapeutic, it would be useful to have a method for causing release of the therapeutic from the microbubbles at a target site.